Abstract: The salivary microbiome plays a crucial role in both oral health and systemic diseases, offering significant insights into disease development and early diagnosis. Under normal conditions, a balanced relationship exists between the microbiota and the host; however, when this balance is disrupted, it can lead to the onset of oral diseases such as dental caries, periodontal disease, and oral cancer. Changes in the salivary microbiome provide valuable information for the early diagnosis of oral diseases. Moreover, microbial dysbiosis in the oral cavity may promote the translocation of pathogenic microorganisms via the gastrointestinal tract, lungs, or bacteremia, leading to ectopic colonization outside the oral cavity and contributing to the onset and progression of systemic diseases such as colorectal cancer, cardiovascular diseases, and autoimmune disorders. Therefore, this review summarizes the role of the salivary microbiome in disease development and diagnosis, based on recent advancements in research on salivary microbiota, offering new perspectives for the early prevention and clinical management of systemic diseases.